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P38, a subtype of mitogen activated protein kinase is essential for the differentiation of skeletal muscle cells


, : P38, a subtype of mitogen activated protein kinase is essential for the differentiation of skeletal muscle cells. FASEB Journal 15(5): A1162, March 8

Myogenesis is regulated by extracellular growth factors. Some of these growth factors induce mitogen activated protein kinase (MAPK) cascade constituted with sub-types of protein kinases, like Erk-1 and -2, p38, SAPK/JNK etc., within muscle cells. But its role had been controversial. Studies on skeletal muscle cell lines like, C2C12, and L6, depicts either no effect or opposite effects of MAPK on myogenesis. The objective of present study was to pin point sub-type specific role of MAPK in myogenesis, if any. To execute that, activities of enzymes, obtained from the rat skeletal muscle cell line, L6E9 cultured in vitro, were analysed by immunocomplex protein kinase assay, western immunoblotting and immunofluorescence microscopy. We show that Erk1/2 activities increased conconcomitantly along with differentiation spanning over four days. The expression of ERK1/2 remained unaltered during myogenesis. Addition of specific inhibitor of Erks, PD098059, to myoblasts resulted in increase in differentiation as determined by the increase in the expression of muscle specific marker proteins, like, myogenin and myosin. However, the creatine kinase activity, a marker of muscular differentiation, did not corroborate with the same observation. In contrast, p38 MAPK activity was activated upto 2.5-folds on the fourth day. The expression of p38 remained unchanged during differentiation. Inhibition of p38 by a specific inhibitor, SB203580, completely abolished myotube formation and expression of myogenin. Moreover, there was a drastic reduction in creatine kinase activity and myosin expression. Our results show that both ERKs and p38 MAPK, are activated during L6E9 differentiation. However, p38MAPK pathway is essential for terminal differentiation in L6E9 myotubes.

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